Methotrexate toxicity and efficacy during the consolidation phase in paediatric acute lymphoblastic leukaemia and MTHFR polymorphisms as pharmacogenetic determinants

D’Angelo, Velia; Ramaglia, M; Iannotta, Adriana; Crisci, Stefania; Indolfi, Paolo; Francese, Matteo; Affinita, Maria Carmen; Pecoraro, Giuseppe; Napolitano, A.; Fusco, Claudia; Oreste, Matilde; Indolfi, Cristiana; Casale, Fiorina

doi:10.1007/s00280-011-1665-1

Cited by 45 publications

(37 citation statements)

References 23 publications

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“…An earlier similar study showed patients with the MTHFR 677CC genotype had a trend of longer TTP (but not response) to cisplatin/gemcitabine in Stage IV NSCLC (Alberola et al, 2004). Other recent reports showed that acute lymphoblastic leukaemia (ALL) patients with 677TT genotype had a significantly higher incidence of relapse compared to other genotypes after the consolidation methotrexate therapy (D′Angelo et al, 2011;Salazar et al, 2011). However, other studies showed MTHFR 677T allele carriers had a higher response rate to 5-FU-based chemotherapy (Cohen et al, 2003;Fernández-Peralta et al, 2010) or FOLFOX therapy (Etienne-Grimaldi et al, 2010).…”

Section: Discussionmentioning

confidence: 96%

Methylenetetrahydrofolate reductase C677T polymorphism predicts response and time to progression to gemcitabine-based chemotherapy for advanced non-small cell lung cancer in a Chinese Han population

Hong

Wang

Zhang

et al. 2013

J. Zhejiang Univ. Sci. B

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Abstract:Objective: The aim of this study was to evaluate the association between the methylenetetrahydrofolate reductase (MTHFR) C677T excision repair cross-complementation group 1 (ERCC1) genetic polymorphisms and the clinical efficacy of gemcitabine-based chemotherapy in advanced non-small cell lung cancer (NSCLC). Methods: A total of 135 chemonaive patients with unresectable advanced NSCLC were treated with gemcitabine/platinum regimens. The polymorphisms of MTHFR C677T, ERCC1 C8092A, and ERCC1 C118T were genotyped using the TaqMan methods. Results: The overall response rate was 28.9%. Patients with MTHFR CC genotype had a higher rate of objective response than patients with variant genotype (TT or CT) (41.2% versus 19.1%, P=0.01). Median time to progression (TTP) of patients with MTHFR CC genotype was longer than that of patients with variant genotype (7.6 months versus 5.0 months, P=0.003). No significant associations were obtained between ERCC1 C118T and C8092A polymorphisms and both response and survival. Conclusions: Our data suggest the value of MTHFR C677T polymorphism as a possible predictive marker of response and TTP in advanced NSCLC patients treated with gemcitabine/platinum.

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Section: Discussionmentioning

confidence: 96%

Methylenetetrahydrofolate reductase C677T polymorphism predicts response and time to progression to gemcitabine-based chemotherapy for advanced non-small cell lung cancer in a Chinese Han population

Hong

Wang

Zhang

et al. 2013

J. Zhejiang Univ. Sci. B

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“…They observed that patients with 5 g/m 2 MTX had a lower frequency of suffering an event than that the patients treated with 3 g/ m 2 MTX (677C+1298A vs. 677 T+1298C, P=0.012) in the consolidation phase. However, D'Angelo et al [72] did not find any difference between 2 and 5 g/m 2 MTX during consolidation phase.…”

Section: Methylenetetrahydrofolate Reductasementioning

confidence: 97%

Gene polymorphisms in the folate metabolism and their association with MTX-related adverse events in the treatment of ALL

Yang

Shen

2015

Tumor Biol.

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The antifolate drug methotrexate (MTX) is widely used in the treatment of various neoplastic diseases, including acute lymphoblastic leukemia (ALL). MTX significantly increases cure rates and improves patients' prognosis. Despite that it achieved remarkable clinical success, a large number of patients still suffer from treatment toxicities or side effects. Even to this date, chemotherapeutic regiments have not been personalized because of interindividual differences that affect MTX response, especially polymorphisms in key genes. The pharmacological pathway of MTX in cells is useful to identify gene polymorphisms that influence the process of treatment. The aim of this review was to discuss the gene polymorphisms of drug-metabolizing enzymes in the MTX pathway and their toxicities on ALL treatment.

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“…Therefore, patients with decreased MTHFR activity are at an increased risk of MTX-related toxicity. The analysis shows that patients with 677TT genotype had a 13 fold increased risk of developing non-hahematological toxicity in the 2 gram MTX dose subgroup when compared to other genotypes and doses [5].…”

Section: Mthfrmentioning

confidence: 99%

Pharmacogenetic Testing for Methotrexate Treatment in Leukemia Patients

Shawaqfeh¹

2016

J Biomol Res Ther

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Methotrexate toxicity and efficacy during the consolidation phase in paediatric acute lymphoblastic leukaemia and MTHFR polymorphisms as pharmacogenetic determinants

Abstract: Our study provides further evidence of the critical role played by folate pathway enzymes in the outcome of ALL, possibly through the interference of MTX.

Cited by 45 publications

References 23 publications

Methylenetetrahydrofolate reductase C677T polymorphism predicts response and time to progression to gemcitabine-based chemotherapy for advanced non-small cell lung cancer in a Chinese Han population

Methylenetetrahydrofolate reductase C677T polymorphism predicts response and time to progression to gemcitabine-based chemotherapy for advanced non-small cell lung cancer in a Chinese Han population

Gene polymorphisms in the folate metabolism and their association with MTX-related adverse events in the treatment of ALL

Pharmacogenetic Testing for Methotrexate Treatment in Leukemia Patients

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